The cell envelope of M. tuberculosis is the focus, and, specifically, in the case of Project 1, fatty acid and mycolic acid anabolism and transfer and the exploitation of promising SB lead compounds, and, in the case of Project 2, inhibition of mycolic acid synthesis and deposition. Project 3 addresses the virgin area of isoprenoid biosynthesis, especially its unique bacterial/mycobacterial features in light of the action of azole compounds and other known antagonists of isoprenoid biosynthesis. Project 4 sharply focuses, for purposes of drug discovery, on the magnum opus of past NCDDG-01 support, i.e., the full elucidation of the biosynthesis of the cell wall arabinogalactan-linker unit, with its array of unique Rhap, Galf and Araf synthetic enzymes and corresponding glycosyltransferases.